Plaunotol [(2E,6Z,10E)-7-hydroxymethyl-3,11,15-trimethyl-2,6,10,14- hexadecatetraen-1-ol], a new anti-ulcer drug, was investigated for its effect on prostaglandin (PG) production. In cultured cells of 3T6 fibroblasts, plaunotol and its main metabolite (1-carboxylic plaunotol) at concentrations of 10-100 microM increased PGE2 and PGI2 production 2- to 4-fold. These compounds increased the release of radioactive arachidonic acid from [14C]arachidonic acid prelabeled 3T6 fibroblast cells 2-fold at 30 microM, and this increase was inhibited by addition of mepacrine, a phospholipase inhibitor. Plaunotol and its main metabolite had no effect on PG cyclooxygenase activity. These results indicate that plaunotol and its main metabolite stimulate PG production by activating cellular phospholipase. In gastric-mucosa slices, PGE2 and PGI2 production was increased significantly either by oral administration of plaunotol to rats at a dose of 300 mg/kg or by addition of the main metabolite to the incubation medium. All these results suggest that plaunotol increases the PG levels in gastric mucosa by stimulating the PG biosynthesis, particularly the cellular phospholipase activity. The increased levels of PG may participate in the anti-ulcer activity of plaunotol.